Cyclic AMP Levels during Stimulation and Inhibition of Histamine Release from Rat Mast Cells by the Calmodulin Inhibitor Trifluoperazine

Abstract

The calmodulin inhibitor trifluoperazine represses compound 48/80-induced histamine release. The effects appear to take place at a step distal to the entrance of calcium into the cell. Trifluoperazine in itself induces histamine release from rat peritoneal mast cells. This release is totally independent of extracellular calcium and at high concentrations of the drug (≥20 μ M), it is due to lysis of the cells. Trifluoperazine reduces the compound 48/80-induced decrease in mast cell cyclic AMP content, probably by inhibiting a cyclic nucleotide phosphodiesterase. The trifluoperazine-induced repression of histamine release does not seem to be correlated to the ability of the drug to alter the compound 48/80 induced changes in cyclic AMP.